44,046 research outputs found

    Specific lid-base contacts in the 26s proteasome control the conformational switching required for substrate degradation.

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    The 26S proteasome is essential for proteostasis and the regulation of vital processes through ATP-dependent degradation of ubiquitinated substrates. To accomplish the multi-step degradation process, the proteasomes regulatory particle, consisting of lid and base subcomplexes, undergoes major conformational changes whose origin is unknown. Investigating the Saccharomyces cerevisiae proteasome, we found that peripheral interactions between the lid subunit Rpn5 and the base AAA+ ATPase ring are important for stabilizing the substrate-engagement-competent state and coordinating the conformational switch to processing states upon substrate engagement. Disrupting these interactions perturbs the conformational equilibrium and interferes with degradation initiation, while later processing steps remain unaffected. Similar defects in early degradation steps are observed when eliminating hydrolysis in the ATPase subunit Rpt6, whose nucleotide state seems to control proteasome conformational transitions. These results provide important insight into interaction networks that coordinate conformational changes with various stages of degradation, and how modulators of conformational equilibria may influence substrate turnover

    CloudTree: A Library to Extend Cloud Services for Trees

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    In this work, we propose a library that enables on a cloud the creation and management of tree data structures from a cloud client. As a proof of concept, we implement a new cloud service CloudTree. With CloudTree, users are able to organize big data into tree data structures of their choice that are physically stored in a cloud. We use caching, prefetching, and aggregation techniques in the design and implementation of CloudTree to enhance performance. We have implemented the services of Binary Search Trees (BST) and Prefix Trees as current members in CloudTree and have benchmarked their performance using the Amazon Cloud. The idea and techniques in the design and implementation of a BST and prefix tree is generic and thus can also be used for other types of trees such as B-tree, and other link-based data structures such as linked lists and graphs. Preliminary experimental results show that CloudTree is useful and efficient for various big data applications

    One machine, one minute, three billion tetrahedra

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    This paper presents a new scalable parallelization scheme to generate the 3D Delaunay triangulation of a given set of points. Our first contribution is an efficient serial implementation of the incremental Delaunay insertion algorithm. A simple dedicated data structure, an efficient sorting of the points and the optimization of the insertion algorithm have permitted to accelerate reference implementations by a factor three. Our second contribution is a multi-threaded version of the Delaunay kernel that is able to concurrently insert vertices. Moore curve coordinates are used to partition the point set, avoiding heavy synchronization overheads. Conflicts are managed by modifying the partitions with a simple rescaling of the space-filling curve. The performances of our implementation have been measured on three different processors, an Intel core-i7, an Intel Xeon Phi and an AMD EPYC, on which we have been able to compute 3 billion tetrahedra in 53 seconds. This corresponds to a generation rate of over 55 million tetrahedra per second. We finally show how this very efficient parallel Delaunay triangulation can be integrated in a Delaunay refinement mesh generator which takes as input the triangulated surface boundary of the volume to mesh
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